Targeting cell-intrinsic and cell-extrinsic mechanisms of intravasation in invasive breast cancer.

The survival of breast cancer patients with metastatic disease has not markedly improved over recent decades, highlighting the need to better understand this process. In this issue of Science Signaling, Pignatelli et al. used freshly obtained invasive ductal carcinoma cells from patients to demonstrate the need for high abundance of the invasive isoform of the Mena protein (Mena(INV)) in cancer cells and colony-stimulating factor 1 (CSF-1)-mediated paracrine signaling in macrophages for efficient transendothelial migration and metastasis formation in all clinical breast cancer subtypes. Furthermore, the triple negative and HER2(+) subtypes, but not the ERPR(+)/HER2(-) subtype, had high CSF-1 receptor (CSF-1R) abundance and also partially used autocrine CSF-1/CSF-1R signaling for invasion. These data establish Mena(INV), CSF-1/CSF-1R, and macrophages as potential therapeutic targets for most human breast cancers.